Tocilizumab in the treatment of rapidly evolving COVID-19 pneumonia and multifaceted critical illness: A retrospective case series

Abstract

Background COVID-19 associated critical illness characterized by rapidly evolving acute respiratory failure (ARF) can develop, especially on the grounds of hyperinflammation. Aim and methods A case-series of 61 patients admitted to our intensive care unit (ICU) between August 12 and September 12, 2020 with confirmed COVID-19 pneumonia and rapidly evolving ARF requiring oxygen support therapy and/or mechanical ventilation was retrospectively analyzed. We examined whether intravenous administration of tocilizumab, a monoclonal interleukin-6 receptor antibody, was associated with improved outcome. All patients received empiric antivirals, dexamethasone 6 mg/day for 7 days, antibiotics, and prophylactic anticoagulation. Tocilizumab was administered at a dosage of 8 mg/kg [two consecutive intravenous infusions 12 h apart]. Outcome measures such as mortality on day-14, ICU length of stay, and rate of nosocomial acquired bacterial infections were also analyzed. Results: Patients were males (88.2%) aged 51 [interquartile range (IQR): 42.5–58.75)], with admission Acute Physiology and Chronic Health Evaluation (APACHE) 4 score of 53 (IQR: 37.75–72.5), and had more than one comorbidity (62.3%). On admission, twenty nine patients (47.5%) were mechanically ventilated, and thirty two patients (52.5%) were receiving oxygen therapy. No serious adverse effects due to tocilizumab therapy were recorded. However, twelve patients (19.6%) developed nosocomial acquired infections. ICU length of stay was 13 (IQR: 9–17) days, and mortality on day-14 was 24.6%. Six patients were shifted to other hospitals but were followed-up. The overall mortality on day-30 was 31.1%. Non-mechanically ventilated patients had higher survival rates compared to mechanically ventilated patients although results were not significant [hazards ratio = 2.6 (95% confidence intervals: 0.9–7.7), p = 0.08]. Tocilizumab did not affect the mortality of critically ill COVID-19 patients. Conclusion Tocilizumab could be an adjunct safe therapy in rapidly evolving COVID-19 pneumonia and associated critical illness.

Therapeutic plasma exchange in patients with life-threatening COVID-19: a randomised controlled clinical trial

“…For example, upon ICU admission, TPE patients had significantly higher incidence of PE and more criteria for developing CRS compared to controls. The pivotal role of IL-6 in the development of CRS was outlined in previous studies using tocilizumab, a monoclonal antibody against IL-6 [ 16 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. Although we showed a decrease in IL-6 following TPE 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , inflammatory biomarkers also decreased over time in controls, as would be expected in any patient that recovers.…”

Tocilizumab Effect in COVID-19 Hospitalized Patients: A Systematic Review and Meta-Analysis of Randomized Control Trials

“…In this review we included a total of 6326 patients from 9 RCTs that compared receiving TCZ plus standard of care (3272 patients) to standard of care alone (3054 patients) in the management of hospitalized COVID-19 pneumonia. The intuition of a presumed benefit of Il-6 receptor antagonists arisen early in the COVID-19 era in view of similarities of the pathophysiology of COVID-19 pneumonia to other conditions associated with cytokine release syndrome, such as haemophagocytic lymphohistiocytosis and macrophage activation syndrome [24] and that this cytokine release syndrome is responsible for the multi-organ failure commonly associated with COVID-19 infection, particularly its severe forms [24] , accordingly, the use of humanized monoclonal antibodies against IL-6 receptors such as TCZ may mitigate the dysregulated host immune response in COVID-19 infection, and subsequently avoid associated lung tissue damage [5] .…”

“…Although, different mortality reports were coming, most of the deaths were attributed to severe COVID-19 cases [4] . COVID-19 is a novel emerging infectious disease associated with a complicated pathogenesis; however, laboratory evidence of severe COVID-19 infections suggests that cytokine release syndrome (CRS) plays a crucial pathogenic role [5] . Although many proinflammatory cytokines are involved in CRS, interleukin-6 (IL-6) is the most important, although it was also found to be a poor prognostic factor [6] .…”

The Role of Convalescent Plasma and Tocilizumab in the Management of COVID-19 Infection: A Cohort of 110 Patients from a Tertiary Care Hospital in Oman

“…A recombinant humanized monoclonal antibody of the IgG1 class, which is directed against both the soluble and membrane-bound forms of the IL-6 receptor, tocilizumab, has been postulated as a potential blocking target to "calm" the cytokine storm in critically ill patients [7][8][9]. Tocilizumab has shown effectiveness and safety in several case reports and small retrospective studies in severe SARS-CoV-2 [10][11][12][13][14][15][16][17], but to date no published randomized clinical trials. To solidify the evidence on the effectiveness and safety of immunomodulating therapies, 110 patients diagnosed with severe COVID-19 from the Royal Hospital (RH) in Oman were recruited and allocated either to standard care and Convalescent Plasma (CP) or standard care and combination CP with Tocilizumab therapy (CPT).…”